Febrile-Range Temperature Modifies Early Systemic Tumor Necrosis Factor Alpha Expression in Mice Challenged with Bacterial Endotoxin

Abstract

Fever improves survival in acute infections, but the effects of increased core temperature on host defenses are poorly understood. Tumor necrosis factor alpha (TNF-α) is an early activator of host defenses and a major endogenous pyrogen. TNF-α expression is essential for survival in bacterial infections but, if disregulated, can cause tissue injury. In this study, we show that passively increasing core temperature in mice from the basal (36.5 to 37.5°C) to the febrile (39.5 to 40°C) range modifies systemic TNF-α expression in response to bacterial endotoxin (lipopolysaccharide). The early TNF-α secretion rate is enhanced, but the duration of maximal TNF-α production is shortened. We identified Kupffer cells as the predominant source of the excess TNF-α production in the warmer animals. The enhanced early TNF-α production observed at the higher temperature in vivo could not be demonstrated in isolated Kupffer cells or in precision-cut liver slices in vitro, indicating the participation of indirect pathways. Therefore, expression of the endogenous pyrogen TNF-α is regulated by increments in core temperature during fever, generating an enhanced early, self-limited TNF-α pulse.

Short-term dietary curcumin supplementation reduces gastrointestinal barrier damage and physiological strain responses during exertional heat stress

“…These may have been afforded through several mechanisms, including: 1) reinforcement of intestinal defenses against gram-negative bacteria; 2) stimulation of anti-inflammatory function; and 3) reductions in apoptosis and oxidative stress. Passive elevation of core temperature in the febrile range is recognized to enhance LPS-induced inflammation (15,36), primarily via increased secretion of proinflammatory cytokines (TNF-␣, IL-1␤, and IL-6) from liver Kupffer cells (16). Neutrophils coordinate the front lines of host defense against gram-negative bacterial infection (41), with neutrophil chemotaxis being stimulated by the release of IL-1␤ and IL-17 from intestinal cells (28,31).…”

Inhibition of Inducible Nitric Oxide Synthase Attenuates Acute Endotoxin‐induced Lung Injury in Rats

“…The assay was calibrated using authentic MG (M0377; Sigma). Tumour necrosis factor‐α and IL‐1β were measured with antibody enzyme‐linked immunosorbent assays (ELISAs) using a commercial antibody pair, recombinant standards and a biotin–streptavidin–peroxidase detection system (Endogen, Rockford, IL, USA) 30 . All reagents, samples and working standards were prepared at room temperature according to the manufacturer's instructions.…”

Regulation of a lymphocyte–endothelial–IL-6 trans-signaling axis by fever-range thermal stress: Hot spot of immune surveillance

“…[84][85][86][91][92][93][94][95][96][97][98]. While heat alone has little effect on the production of pro-inflammatory cytokines, it can act in conjunction with strong inflammatory stimuli like bacterial LPS to increase the synthesis of IL-6, TNF, IFN-α, GM-CSF, G-CSF and CXC chemokines [84,92,[99][100][101][102][103]. Conversely, thermal stress has also been proposed to play a role in the resolution of inflammatory responses through the downregulation of cytokine production [84,[104][105][106].…”